An objective of a variety of medical applications is to selectively compromise or destroy vascular function. One such application is the treatment of solid tumors. It has been shown that a reduction in tumor blood flow reduces nutrients to the tumor and causes accumulation of catabolite products and extracellular acidification, all of which result in a cascade of tumor cell death. Brown, J. M., Exploitation of bioreductive agents with vasoactive drugs, In Fiedlen E. M., Fowler J. F., Hendry J. H., Scott D., eds. Proceedings of the Eight International Congress on Radiation Research, Edinburg UK, Vol. 2, London, Taylor and Francis, 1987, 719-724; Chaplin D J, Acker B., The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069: evidence for therapeutic gain; Int J Radiant Oncol Biol Phys 1987, 13, 579-585; Stratford I. J., Adams G. E., Godden J., Nolan J., Howells N., Timpson N.; Potentiation of the anti-tumor effect of melphalan by the vasoactive agent, hydralazine. Br. J. Cancer 1988, 58, 122-127; Denekamp J, Hill S A, Hobson B, Vascular occlusion and tumor cell death, Eur. J. Cancer Clin. Oncol. 1983, 19, 271-275.
One approach to creating vascular dysfunction involves inducing tumor-selective thrombosis that shuts down the blood supply to the tumor cells (S. Ran, B. Gao, S. Duffy, L. Watkins, N. Rote, P. E. Thorpe, Cancer Res. 58 (1998) 4646-3653; F. Nilsson, H. Kosmehl, L. Zardi, D. Neri, Cancer Res. 61 (2001) 711-716). There are many anticancer drugs and agents which have been shown to cause such thrombosis, including cytokines (P. L. J. Naredi, P. G. Lindner, S. B. Holmberg, U. Stenram, A. Peterson and L. R. Hafstrom, The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma, Int. J. Cancer 54 (1993), pp. 645-649; F. Kallinowski, C. Schaefer, G. Tyler and P. Vaupel, In vivo targets of recombinant human tumor necrosis factor-a: blood flow, oxygen consumption and growth of isotransplanted rat tumours; Br. J. Cancer 60 (1989), pp. 555-560; P. G. Braunschweiger, C. S. Johnson, N. Kumar, V. Ord and P. Furmonski, Antitumor effects of recombinant human interleukin 1α in RIF-1 and PancO2 solid tumors, Cancer Res. 48 (1988), pp. 6011, 6016), serotonin, flavone acetic acid (D. J. Chaplin, The effect of therapy on tumor vascular function; Int. J. Radiat. Biol. 60 (1991), pp. 311, 325) and vinca alkaloids (S. A. Hill, L. E. Sampson and D. J. Chaplin, Anti-vascular approaches to solid tumor therapy: evaluation of vinblastine and flavone acetic acid; Int. J. Cancer 63 (1995), pp. 119-123). However, the effectiveness of many of these agents is limited by the risk of unacceptable system toxicity (G. Sersa, M. Cemasar, C. S. Parkins and D. J. Chaplin: Tumor blood flow changes induced by application of electric pulses, European Journal of Cancer 35, N. 4, (1999) pp. 672-677), among other factors.
Various other types of therapies have also been shown to affect some degree of vascular dysfunction in tumors, including hyperthermia (C. W. Song, Effect of local hyperthermia on blood flow and microenvironment, Cancer Res. 44 (1984), pp. 4721-4730), photodynamic therapy (V. H. Fingar and B. W. Henderson, Drug and light dose dependence of photodynamic therapy: a study of tumour and normal tissue response. Photochem. Photobiol. 46 (1987), pp. 837-841) and high-energy shock wave therapy (F. Gamarra, F. Spelsberg, G. E. H. Kuhnle and A. E. Goetz, High-energy shock waves induce blood flow reduction in tumors, Cancer Res. 53 (1993), pp. 1590-1595). However, complete and permanent hemostasis has not yet been achieved by these methodologies. Mechanical clamping of the tumor-supporting vasculature has also been proposed (Denekamp J, Hill S. A., Hobson B., Vascular occlusion and tumor cell death, Eur. J. Cancer Clin. Oncol. 1983, 19, 271-275), however, such technique may be impractical due to the extremely twisted and branched nature of tumor vasculature.
Another application involving the selective destruction of vascular function is in the treatment of cutaneous vascular disorders, such as telangiectasia (commonly known as “spider veins”) and in the removal of cutaneous vascular lesions, e.g., capillary hemangiomas (such as cafe-au-lait spots and port wine stains). These conditions all involve dilated or engorged capillaries in the skin. While not often of physical concern, they can be unsightly and cause emotional distress to the patient.
The most common treatment used for cutaneous vascular lesions is sclerotherapy, which entails the intravascular injection of one of a variety of agents into the abnormal blood vessels. The injected substance injures the interior walls of the capillary causing it to shrink or disappear. Unfortunately, this treatment can be painful, only partially effective, and usually requires about one to two months before improvement can be seen. In addition, undesirable side effects can occur, such as echymotic or hyperpigmented marks, which may take months to completely fade away.
Other treatments such as freezing, surgery, radiation, phototherapy and laser therapy have also been employed for subcutaneous and cutaneous vascular conditions. Of these, the use of lasers has been the most successful as the destruction of the offending capillaries is achieved with the least amount of damage to the overlying skin. However, laser therapy is not without its shortcomings. The blood hemoglobin absorbs the laser light and the resulting hyperthermia leads to coagulation of the blood within the vessels in the surface layer of the skin. Where the affected skin area is relatively deep, the more superficial capillaries absorb the majority of the light energy and the remaining energy is insufficient to effectively treat the deeper vessels (referred to as “shadowing”). This problem can be solved to some degree by use of less absorbent wavelengths, however, this is at the sake of a reduced ability to localize heat, which may necessitate longer treatments and/or multiple treatments which are both expensive and time-consuming. Additionally, laser therapy does not work as well with patients having a darker skin pigment as the epidermal melanin absorbs a significant portion of the light to which it is exposed, thus, reducing the amount of light that is able to reach the blood. The increase in the intensity of the laser required to compensate for interference from tissue and melanin may lead to thermal injury of the skin and to post-inflammatory pigment changes.
Many recent improvements in electrosurgical technology, particularly in bipolar electrosurgical devices, have made it easy to use in surgical and other therapeutic settings. Ostensibly, electrosurgery may be a viable alternative to the above-described modalities for treating tumors and cutaneous and subcutaneous vascular disorders. However, current electrosurgical devices and procedures are based on the thermal denaturation and coagulation of tissues and still suffer from significant thermal damage to surrounding tissue, and an inability to accurately control the depth of necrosis in the tissue being treated. Additionally, the application of current to tissue results in electrochemical reactions which lead to the accumulation of toxic products on the electrodes that may cause cytolysis of the surrounding tissue (Peterson H. I., Tumor Blood Circulation Angiogenesis, Vascular Morphology and Blood Flow of Experimental and human tumors, Florida, CRC Press, 1979, 1-229). In addition, hydrolysis on the electrodes emits gases which may interfere with current transmission, making the treatment unpredictable and unstable (S. Guarini, A Highly Reproducible Model of Arterial Thrombosis in Rats, Journal of Pharmacological and Toxicological Methods, 35 (1996) pp 101-105). These shortcomings are particularly significant in applications in which the target area is extremely small, e.g., capillary vessels having diameters in the range from about 10 to about 100 μm.
Accordingly, there is still a need for improved methodologies for creating hemostasis within blood vessels without causing damage to adjacent tissue. In particular, there is a need for a more effective and safe way to treat solid tumors and cutaneous and subcutaneous vascular disorders.